title: Graves' disease following thyrotoxic painless thyroiditis. Analysis of antibody activities against the thyrotropin receptor in two cases.
abstract: The exact immunologic mechanisms that lead to the emergence and progression of painless ("silent") thyroiditis remain unclear. We report two cases of painless postpartum thyroiditis followed by Graves' disease, where extensive immunologic evaluation supported a possible pathogenetic association. The time course of changes in thyroid function tests, 123I thyroidal uptake values, and thyrotropin receptor antibodies (TSHRAbs) were documented. The existence of stimulating TSHRAbs (TSAbs) activating the cyclic adenosine monophosphate (cAMP) and phosphatidylinositol 4,5-bisphosphate (PIP2) signal cascades and their functional epitopes, as well as two different thyrotropin-binding inhibitory immunoglobulins (TBII) were documented in both patients at the time of diagnosis of Graves' disease. We suggest that susceptible persons may develop an immunologic response that can trigger the appearance of a mixture of species of TSHRAbs, which in turn may lead to the sequential occurrence of painless thyroiditis and Graves' disease. Additionally, the multiple phases of hyperthyroidism and hypothyroidism that can occur in these patients may reflect the existence and changing spectrum of TSHRAbs in their sera.
authors.affiliation: Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0805, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Sarlis
authors.forename: F
authors.initials: F
authors.lastname: Brucker-Davis
authors.forename: J P
authors.initials: JP
authors.lastname: Swift
authors.forename: K
authors.initials: K
authors.lastname: Tahara
authors.forename: L D
authors.initials: LD
authors.lastname: Kohn
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D000242:Cyclic AMP / Q000276:immunology / Q000378:metabolism; D005260:Female; D006111:Graves Disease / Q000209:etiology* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000276:immunology / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology; D013958:Thyroid Crisis / Q000150:complications; D013966:Thyroiditis / Q000209:etiology* / Q000276:immunology
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D019269:Phosphatidylinositol 4,5-Diphosphate; D011989:Receptors, Thyrotropin; D000242:Cyclic AMP